Keratinocytes cut corners on the cell cycle for the sake of skin barrier integrity

Hou, Renzhi; Kim, Jung Eun; Plikus, Maksim V.

doi:10.1016/j.devcel.2022.06.001

Cited by 2 publications

(1 citation statement)

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“…Due to the role of Shh signaling in the pathogenesis of basal cell carcinoma of the skin, the role of Kif7 has been studied in keratinocytes. This work has been primarily performed in the mouse as the model system; however, studies within the zebrafish have shown similarities of epidermal ontogeny [54,55]. In keratinocytes, Kif7 has been shown to have a crucial role as a positive regulator of Shh signaling through its regulatory function of the Gli transcription factors [56].…”

Section: Discussionmentioning

confidence: 99%

Cytoskeletal Keratins Are Overexpressed in a Zebrafish Model of Idiopathic Scoliosis

Cuevas

Terhune

Wethey

et al. 2023

Genes

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Idiopathic scoliosis (IS) is a three-dimensional rotation of the spine >10 degrees with an unknown etiology. Our laboratory established a late-onset IS model in zebrafish (Danio rerio) containing a deletion in kif7. A total of 25% of kif7co63/co63 zebrafish develop spinal curvatures and are otherwise developmentally normal, although the molecular mechanisms underlying the scoliosis are unknown. To define transcripts associated with scoliosis in this model, we performed bulk mRNA sequencing on 6 weeks past fertilization (wpf) kif7co63/co63 zebrafish with and without scoliosis. Additionally, we sequenced kif7co63/co63, kif7co63/+, and AB zebrafish (n = 3 per genotype). Sequencing reads were aligned to the GRCz11 genome and FPKM values were calculated. Differences between groups were calculated for each transcript by the t-test. Principal component analysis showed that transcriptomes clustered by sample age and genotype. kif7 mRNA was mildly reduced in both homozygous and heterozygous zebrafish compared to AB. Sonic hedgehog target genes were upregulated in kif7co63/co63 zebrafish over AB, but no difference was detected between scoliotic and non-scoliotic mutants. The top upregulated genes in scoliotic zebrafish were cytoskeletal keratins. Pankeratin staining of 6 wpf scoliotic and non-scoliotic kif7co63/co63 zebrafish showed increased keratin levels within the zebrafish musculature and intervertebral disc (IVD). Keratins are major components of the embryonic notochord, and aberrant keratin expression has been associated with intervertebral disc degeneration (IVDD) in both zebrafish and humans. The role of increased keratin accumulation as a molecular mechanism associated with the onset of scoliosis warrants further study.

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Section: Discussionmentioning

confidence: 99%